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Published on : Mar 14, 2014
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Slide 1 - A 36 year old female with a painful, rapidly progressive breast ulcer. ID Case Conference Wednesday, April 11th, 2007 David Fitzgerald, MD
Slide 2 - HPI 36 yo WF 3 months s/p C-section delivery of triplets, complicated by post-op wound infection requiring IV antibiotics, now with a 10 day history of R breast pain and redness. She reports that 10 days prior to presenting to ID clinic she woke up with what she thought was an insect bite on her R breast with a small area of redness and tenderness. Over the next several days this progressed to an abscess and she presented to an urgent care center where an incision and drainage procedure was performed and she was prescribed keflex. Infection initially improved slightly following drainage, however pain increased and purulent material continued to drain from area. She was contacted by the urgent care center and informed that the culture grew MR Staph Aureus and that she should seek further care elsewhere. As she was known to ID service at UNC she contacted service over weekend and was prescibed clindamycin empirically (she has a sulfa allergy). She then developed fever to 101 and came to ID clinic for follow up.
Slide 3 - HPI In ID clinic she was noted to be febrile to 39.7, tachycardic to 140 and hypotensive to 90s/60s. She had a large area of necrotic tissue and erythema over her R lateral breast away from the aerola. Purulence was noted from the wound. IV fluids were started. Labs and Bcx obtained. IV Tigecycline started. Urgent US was performed which did not show an abscess but showed skin thickening and edema. Surgery was consulted and the patient was admitted for IV abx. Pt underwent debridement of necrotic tissue on 3/8 with 10x 10 cm area debrided.
Slide 4 - PMH 1. Post-op C-section wound infection requiring debridement of tissue on post-op day 12. Cxs only grew CNS. Treated with vanco and zosyn, but developed fever after discharge, attributed to vanco. Developed rash to daptomycin started in place of vancomycin. Restarted vancomycin and developed a rash again. Finished outpt course with Linezolid and ertapenem but at end of treatment developed rash. 2. C-section on 12/10/06 with triplets. 3. Two previous episodes of perirectal abscesses in 2001 and 2002. One episode lead to formation of fistula tract to rectum. 4. Shingles in 2002. 5. Status post myomectomy in 12/05. 6. Hypothryoidism. 7. History of recurrent sinusitis.
Slide 5 - SH Works as a computer software developer. Lives with husband and 3 newborns. Denies tobacco, alcohol and illicits. No recent travel. No pets at home. No recent animal contacts. Ethnically of Ashkenazi/Eastern European descent.
Slide 6 - FH Hypertension and hypercholesterol.
Slide 7 - Medications/Allergies Medications Clindamycin 300 mg q.8h. Begun 2 days prior. Levothyroid 112 mcg once daily, Multi vitamin Tylenol p.r.n. Allergies Bactrim – resp distress Vanco – rash, ? Fever Daptomycin – Rash Linezolid - Rash
Slide 8 - Physical Exam Pleasant young woman in moderate distress T 39.7 P 140 BP 90/60, RR 18, Sat 98% RA HEENT Perrla, EOMI, anicteric, mucous membranes dry Neck Supple Lymph – no cervical, sc lan CV – Tachy, regular, no mrg Lungs – CTAB Breast – R breast with 7 x 8 cm area of necrotic tissue with dark edges and 1-2 cm surrounding erythema. Purulent drainage from wound but no appreciable deep abscess. Exceedingly tender to palpation.
Slide 9 - Data WBC 24 K ANC 22.4 ALC 1.0 HGB 12.6 Plts 395 ESR 48 Basic WNL with BUN/Cr of 18/0.8 LFTs WNL Micro Wound swab – 2+ PMNs, no organisms, no growth. BCX x 2 – No growth Ucx – no growth Prior breast abscess from 5 days prior revealed MRSA sensitive to clinda (negative for inducible resistance), bactrim, vancomycin, gentamicin and tetracycline
Slide 10 - Hospital course Patient remained ill with continued tachycardia and hypotension requiring fluid support for 5 more days. Fevers continued to 39.5. Continued on Tigecycline. Repeat Bcxs negative. Due to extension of area of necrosis she required repeat surgical debridements on 3/11 (16x 15 cm) 3/13 (entire lateral aspect of breast and extending medially) 3/17 (nipple also involved and resected). At each operation was noted to have necrosis and purulence of edge of wound but no deeper infection. CT chest confirmed that there was no deep abscess or fluid collection. By hospital day 6 pt was only having low grade temps (38.1), BP stable and HR down to 80s to 110s but necrosis continued despite clinical improvement.
Slide 11 - Pathology and further micro Surgical path “The two previous debridements have been reviewed. The morphologic appearance of all three lesions is similar, showing large aggregatesof neutrophils accompanied by epidermal ulceration.  Previous special stainshave been negative for bacteria, fungi, and AFB. “ Micro Multiple surgical gram stains and cultures revealed 2 + PMNS, no organisms and no growth. One surgical culture grew coag neg Staph.
Slide 12 - A consultation was obtained…
Slide 13 - Clinical course All cxs remained negative except for one surgical cx with CNS At recommendation of derm, pt was started on prednisone and antibiotics were eventually stopped with halt of progression of necrosis Pt seen in follow up one week after d/c off abx and on prednisone 100 mg daily with clean wound edges and no evidence of purulence Seen also by GI for planned colonoscopy
Slide 14 - Immune function testing Immunoglobulin levels – WNL except slightly high IgE NEUTROPHIL OXIDATIVE INDEX - WNL Not consistent with CGD Leukocyte adhesion deficiency panel WNL HIV negative, CD4 wnl
Slide 15 - Pyoderma gangrenosum A reactive inflammatory dermatosis originally described at Mayo Clinic in 1930. Part of the spectrum of neutrophilic dermatoses – which are reactive processes that have in common: 1. Non-infectious dermal neutrophilia, 2. Usually an associated condition (inflammatory bowel disease, paraproteinemia, or arthritis), 3. A tendency for pathergy - 4. Similarities in treatment (prednisone and dapsone) The neutrophilic dermatoses include acute febrile neutrophilic sermatosis (Sweet’s syndrome), bowel associated dermatosis-arthritis syndrome, neutrophilic eccrine hidradenitis, subcorneal pustular dermatosis (Sneddon-Wilkinson Disease) rheumatoid neutrophilic dermatitis. SAPHO (synovitis, acne, pustulosis, hyperostosis and osteomyelitis) A diagnosis of exclusion. Considered a dermatological emergency.
Slide 16 - Pyoderma gangrenosum Typical course is the rapid progression of a painful, necrolytic ulcer with an irregular, undermined border. Usually begins as a nodule or sterile pustule that progresses to a necrotic and mucopurulent ulcer with an edematous, violaceous, serpiginously expanding undermined red-blue border. The process rapidly destroys skin tissue with a liquefactive necrosis. Usually a 1-2 cm halo of erythema around lesion Usually exceedingly tender (out of proportion to the extent of the ulcer). Most frequently affects the LE but can occur anywhere.
Slide 17 - Diagnosis Diagnosis of exclusion Biopsy necessary to rule out infectious and vasculitic causes
Slide 18 - Major Diagnostic Criteria Rapid progression of a painful, necrolytic cutaneous ulcer with an irregular, violaceous and undermined border Margin expansion of 1 to 2 cm per day or 50% increase in ulcer size in one month Pain usually out or proportion to size of ulceration Ulcer typically preceded by a papule, pustule or bulla Other causes of cutaneous ulceration have been excluded Usually necessitates skin biopsy
Slide 19 - Minor Diagnostic Criteria History suggestive of pathergy or clinical finding of cribriform scarring Ulcer development at sites of minor cutaneous trauma Systemic diseases associated with PG Inflammatory bowel disease, arthritis, IgA gammopathy, or underlying malignancy Histopathological findings sterile dermal neutrophilia, mixed inflammation, lymphocytic vasculitis Treatment response Rapid response to systemic steroid treatment
Slide 20 - Associated conditions Occur in 70% of cases of PG Inflammatory bowel disease Seropositive or seronegative arthritis Myeloma Paraproteinemia Diverticulitis Malignancy (leukemia)
Slide 21 - Pathology Mixed cellular inflammation with neutrophil predominance
Slide 22 - Differential Diagnosis Vascular occlusion or stasis Antiphospholipid-antidoby syndrome Livedoid vasculopathy Venous stasis ulceration Klippel_Trenaunay_Weber syndrome Small vessel occlusive arterial disease Type 1 cryoglobulinemia
Slide 23 - Differential Diagnosis Vasculitis Wegener granulomatosis Polyarteritis nodosa Cryoglobulinemic vasculitis Takayasu arteritis Leukocytoclastic vasculitis
Slide 24 - Differential Diagnosis Malignant cutaneous involvement Angiocentric T-cell lymphoma Anaplastic large-cell T-cell lymphoma Mycosis fungoides bullosa Unspecified lymphoma Leukemia cutis Histiocytosis X (Langerhans cell histiocytosis)
Slide 25 - Differential Diagnosis Primary cutaneous infection Sporotrichosis Aspergillosis Cryptococcosis Herpes simplex type 2 virus Cutaneous tuberculosis Amebiasis cutis Zygomycosis Penicillum marneffei
Slide 26 - Differential Diagnosis Drug-induced & exogenous tissue injury Munchausen syndrome and factitiousdisorder Hydrea-induced ulceration Bromoderma Contact vulvitis Drug-induced lupus Laxoscelism (Brown recluse spider bite) Injection drug abuse with secondary infection
Slide 27 - Differential Diagnosis Other inflammatory disorders Cutaneous Crohn disease Ulcerative necrobiosis lipoidca
Slide 28 - Treatment Corticosteroids are mainstay of therapy. Usually will have dramatic improvement after 48-72 hours Reduced pain and decreased erythema are the most dramatic markers of response to treatment. Halt of enlargement, less induration and less erythema also occur. Dapsone, cyclosporine, azathioprine, tacrolimus. Topical treatments possible with super-potent steroids in some limited cases. Often require prolonged course of treatment with slow taper of immunosuppression Treatment of underlying disease is also often effective
Slide 29 - Reported Effective Treatments Corticosteroids Systemic, intralesional, topical Antimicrobial agents Benzoyl peroxide, clofazamine, dapsone, rifampicin, lymcycline, tetracycline, minocycline, mezlocillin, Potassium iodide, sulfapyridine, vancomycin
Slide 30 - Reported Effective Treatments Steroid-sparing immunosuppressive agents 5-aminosalicylic acid (topical), 6-mercaptopurine, azathioprine, cholorambucil, cyclophosphamide, cyclosporine( systemic, topical), methotextrate, mycophenolate mofetil, nitrogen mustard (topical), tacrolimus (systemic, topical), melphalan Immune modulation Infliximab, interferon-a, intravenous y-globulin, plasmapheresis Miscellaneous Colchicine, nicotine (topical), sodium cromoglycate (topical)
Slide 31 - Search PubMed Pyoderma Gangrenosum Case Reports Reviews Differential Diagnosis Drug Therapy