a 36 year old female with a painful, rapidly progressive breast ulcer. id case conference wednesday,...

A 36 year old female A 36 year old female with a painful, rapidly with a painful, rapidly

progressive breast ulcer.progressive breast ulcer.

ID Case ConferenceID Case Conference

Wednesday, April 11Wednesday, April 11thth, 2007, 2007

David Fitzgerald, MDDavid Fitzgerald, MD

HPIHPI► 36 yo WF 3 months s/p C-section delivery of triplets, complicated by 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 post-op wound infection requiring IV antibiotics, now with a 10 day history of R breast pain and redness. history of R breast pain and redness.

► She reports that 10 days prior to presenting to ID clinic she woke up 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 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 area of redness and tenderness. Over the next several days this progressed to an abscess and she presented to an urgent care center progressed to an abscess and she presented to an urgent care center where an incision and drainage procedure was performed and she where an incision and drainage procedure was performed and she was prescribed keflex. was prescribed keflex.

► Infection initially improved slightly following drainage, however pain Infection initially improved slightly following drainage, however pain increased and purulent material continued to drain from area. She increased and purulent material continued to drain from area. She was contacted by the urgent care center and informed that the was contacted by the urgent care center and informed that the culture grew MR Staph Aureus and that she should seek further care culture grew MR Staph Aureus and that she should seek further care elsewhere.elsewhere.

► As she was known to ID service at UNC she contacted service over As she was known to ID service at UNC she contacted service over weekend and was prescibed clindamycin empirically (she has a sulfa weekend and was prescibed clindamycin empirically (she has a sulfa allergy). She then developed fever to 101 and came to ID clinic for allergy). She then developed fever to 101 and came to ID clinic for follow up.follow up.

HPIHPI

► In ID clinic she was noted to be febrile to 39.7, In ID clinic she was noted to be febrile to 39.7, tachycardic to 140 and hypotensive to 90s/60s. tachycardic to 140 and hypotensive to 90s/60s. She had a large area of necrotic tissue and She had a large area of necrotic tissue and erythema over her R lateral breast away from the erythema over her R lateral breast away from the aerola. Purulence was noted from the wound. aerola. Purulence was noted from the wound.

► IV fluids were started. Labs and Bcx obtained. IV IV fluids were started. Labs and Bcx obtained. IV Tigecycline started.Tigecycline started.

► Urgent US was performed which did not show an Urgent US was performed which did not show an abscess but showed skin thickening and edema.abscess but showed skin thickening and edema.

► Surgery was consulted and the patient was Surgery was consulted and the patient was admitted for IV abx.admitted for IV abx.

► Pt underwent debridement of necrotic tissue on 3/8 Pt underwent debridement of necrotic tissue on 3/8 with 10x 10 cm area debrided. with 10x 10 cm area debrided.

PMHPMH► 1. Post-op C-section wound infection requiring debridement of 1. Post-op C-section wound infection requiring debridement of

tissue on post-op day 12. Cxs only grew CNS. Treated with tissue on post-op day 12. Cxs only grew CNS. Treated with vanco and zosyn, but developed fever after discharge, vanco and zosyn, but developed fever after discharge, attributed to vanco. Developed rash to daptomycin started in attributed to vanco. Developed rash to daptomycin started in place of vancomycin. Restarted vancomycin and developed a place of vancomycin. Restarted vancomycin and developed a rash again. Finished outpt course with Linezolid and rash again. Finished outpt course with Linezolid and ertapenem but at end of treatment developed rash. ertapenem but at end of treatment developed rash.

► 2. C-section on 12/10/06 with triplets. 2. C-section on 12/10/06 with triplets. ► 3. Two previous episodes of perirectal abscesses in 2001 and 3. Two previous episodes of perirectal abscesses in 2001 and

2002. One episode lead to formation of fistula tract to 2002. One episode lead to formation of fistula tract to rectum. rectum.

► 4. Shingles in 2002. 4. Shingles in 2002. ► 5. Status post myomectomy in 12/05. 5. Status post myomectomy in 12/05. ► 6. Hypothryoidism.6. Hypothryoidism.► 7. History of recurrent sinusitis. 7. History of recurrent sinusitis.

SHSH

►Works as a computer software Works as a computer software developer. Lives with husband and 3 developer. Lives with husband and 3 newborns. newborns.

►Denies tobacco, alcohol and illicits.Denies tobacco, alcohol and illicits.►No recent travel.No recent travel.►No pets at home. No recent animal No pets at home. No recent animal

contacts. contacts. ►Ethnically of Ashkenazi/Eastern European Ethnically of Ashkenazi/Eastern European

descent. descent.

FHFH

►Hypertension and hypercholesterol.Hypertension and hypercholesterol.

Medications/AllergiesMedications/Allergies

►MedicationsMedications Clindamycin 300 mg Clindamycin 300 mg

q.8h. Begun 2 days q.8h. Begun 2 days prior. prior.

Levothyroid 112 mcg Levothyroid 112 mcg once daily, once daily,

Multi vitaminMulti vitamin Tylenol p.r.n. Tylenol p.r.n.

► AllergiesAllergies Bactrim – resp Bactrim – resp

distressdistress Vanco – rash, ? FeverVanco – rash, ? Fever Daptomycin – RashDaptomycin – Rash Linezolid - RashLinezolid - Rash

Physical ExamPhysical Exam

► Pleasant young woman Pleasant young woman in moderate distressin moderate distress

► T 39.7 P 140 BP 90/60, T 39.7 P 140 BP 90/60, RR 18, Sat 98% RARR 18, Sat 98% RA

► HEENT Perrla, EOMI, HEENT Perrla, EOMI, anicteric, mucous anicteric, mucous membranes drymembranes dry

► Neck SuppleNeck Supple► Lymph – no cervical, sc Lymph – no cervical, sc

lanlan

► CV – Tachy, regular, no CV – Tachy, regular, no mrgmrg

► Lungs – CTABLungs – CTAB► Breast – R breast with 7 Breast – R breast with 7

x 8 cm area of necrotic x 8 cm area of necrotic tissue with dark edges tissue with dark edges and 1-2 cm and 1-2 cm surrounding erythema. surrounding erythema. Purulent drainage from Purulent drainage from wound but no wound but no appreciable deep appreciable deep abscess. Exceedingly abscess. Exceedingly tender to palpation. tender to palpation.

DataData

► WBC 24 KWBC 24 K ANC 22.4ANC 22.4 ALC 1.0ALC 1.0

► HGB 12.6HGB 12.6► Plts 395Plts 395

► ESR 48ESR 48► Basic WNL with BUN/Cr Basic WNL with BUN/Cr

of 18/0.8of 18/0.8► LFTs WNLLFTs WNL

► MicroMicro Wound swab – 2+ PMNs, Wound swab – 2+ PMNs,

no organisms, no growth.no organisms, no growth. BCX x 2 – No growthBCX x 2 – No growth Ucx – no growthUcx – no growth

Prior breast abscess from Prior breast abscess from 5 days prior revealed 5 days prior revealed MRSA sensitive to clinda MRSA sensitive to clinda (negative for inducible (negative for inducible resistance), bactrim, resistance), bactrim, vancomycin, gentamicin vancomycin, gentamicin and tetracycline and tetracycline

Hospital courseHospital course► Patient remained ill with continued tachycardia and Patient remained ill with continued tachycardia and

hypotension requiring fluid support for 5 more days. Fevers hypotension requiring fluid support for 5 more days. Fevers continued to 39.5. Continued on Tigecycline. Repeat Bcxs continued to 39.5. Continued on Tigecycline. Repeat Bcxs negative.negative.

► Due to extension of area of necrosis she required repeat Due to extension of area of necrosis she required repeat surgical debridements on surgical debridements on 3/11 (16x 15 cm)3/11 (16x 15 cm) 3/13 (entire lateral aspect of breast and extending medially) 3/13 (entire lateral aspect of breast and extending medially) 3/17 (nipple also involved and resected).3/17 (nipple also involved and resected).

► At each operation was noted to have necrosis and purulence At each operation was noted to have necrosis and purulence of edge of wound but no deeper infection.of edge of wound but no deeper infection.

► CT chest confirmed that there was no deep abscess or fluid CT chest confirmed that there was no deep abscess or fluid collection.collection.

► By hospital day 6 pt was only having low grade temps (38.1), 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 BP stable and HR down to 80s to 110s but necrosis continued despite clinical improvement.despite clinical improvement.

Pathology and further microPathology and further micro

► Surgical pathSurgical path ““The two previous The two previous

debridements have been debridements have been reviewed. The reviewed. The morphologic appearance morphologic appearance of all three lesions is of all three lesions is similar, showing large similar, showing large aggregatesaggregatesof neutrophils of neutrophils accompanied by accompanied by epidermal ulceration. epidermal ulceration. Previous special stains Previous special stainshave been negative for have been negative for bacteria, fungi, and AFB. “bacteria, fungi, and AFB. “

► MicroMicro Multiple surgical gram Multiple surgical gram

stains and cultures stains and cultures revealed 2 + PMNS, no revealed 2 + PMNS, no organisms and no organisms and no growth.growth.

One surgical culture One surgical culture grew coag neg Staph.grew coag neg Staph.

►A consultation was obtained…A consultation was obtained…

Clinical courseClinical course

All cxs remained negative except for one All cxs remained negative except for one surgical cx with CNSsurgical cx with CNS

At recommendation of derm, pt was started on At recommendation of derm, pt was started on prednisone and antibiotics were eventually prednisone and antibiotics were eventually stopped with halt of progression of necrosisstopped with halt of progression of necrosis

Pt seen in follow up one week after d/c off abx Pt seen in follow up one week after d/c off abx and on prednisone 100 mg daily with clean and on prednisone 100 mg daily with clean wound edges and no evidence of purulencewound edges and no evidence of purulence

Seen also by GI for planned colonoscopySeen also by GI for planned colonoscopy

Immune function testingImmune function testing

► Immunoglobulin levels – WNL except Immunoglobulin levels – WNL except slightly high IgEslightly high IgE

►NEUTROPHIL OXIDATIVE INDEX - WNLNEUTROPHIL OXIDATIVE INDEX - WNL Not consistent with CGDNot consistent with CGD

►Leukocyte adhesion deficiency panel Leukocyte adhesion deficiency panel WNLWNL

►HIV negative, CD4 wnlHIV negative, CD4 wnl

Pyoderma gangrenosumPyoderma gangrenosum► A reactive inflammatory dermatosis originally described at Mayo A reactive inflammatory dermatosis originally described at Mayo

Clinic in 1930.Clinic in 1930.► Part of the spectrum of Part of the spectrum of neutrophilic dermatosesneutrophilic dermatoses – which are reactive – which are reactive

processes that have in common:processes that have in common:1. Non-infectious dermal neutrophilia, 1. Non-infectious dermal neutrophilia, 2. Usually an associated condition (inflammatory bowel disease, 2. Usually an associated condition (inflammatory bowel disease,

paraproteinemia, or arthritis), paraproteinemia, or arthritis), 3. A tendency for pathergy - 3. A tendency for pathergy - 4. Similarities in treatment (prednisone and dapsone)4. Similarities in treatment (prednisone and dapsone)

► The The neutrophilic dermatosesneutrophilic dermatoses include include acute febrile neutrophilic sermatosis (Sweet’s syndrome),acute febrile neutrophilic sermatosis (Sweet’s syndrome), bowel associated dermatosis-arthritis syndrome, bowel associated dermatosis-arthritis syndrome, neutrophilic eccrine hidradenitis, neutrophilic eccrine hidradenitis, subcorneal pustular dermatosis (Sneddon-Wilkinson Disease) subcorneal pustular dermatosis (Sneddon-Wilkinson Disease) rheumatoid neutrophilic dermatitis.rheumatoid neutrophilic dermatitis. SAPHO (synovitis, acne, pustulosis, hyperostosis and osteomyelitis)SAPHO (synovitis, acne, pustulosis, hyperostosis and osteomyelitis)

► A diagnosis of exclusion. Considered a dermatological emergency. A diagnosis of exclusion. Considered a dermatological emergency.

Pyoderma gangrenosumPyoderma gangrenosum

► Typical course is the rapid progression of a painful, Typical course is the rapid progression of a painful, necrolytic ulcer with an irregular, undermined border. necrolytic ulcer with an irregular, undermined border.

► Usually begins as a nodule or sterile pustule that Usually begins as a nodule or sterile pustule that progresses to a necrotic and mucopurulent ulcer with progresses to a necrotic and mucopurulent ulcer with an edematous, violaceous, serpiginously expanding an edematous, violaceous, serpiginously expanding undermined red-blue border.undermined red-blue border.

► The process rapidly destroys skin tissue with a The process rapidly destroys skin tissue with a liquefactive necrosis. liquefactive necrosis.

► Usually a 1-2 cm halo of erythema around lesionUsually a 1-2 cm halo of erythema around lesion► Usually exceedingly tender (out of proportion to the Usually exceedingly tender (out of proportion to the

extent of the ulcer).extent of the ulcer).► Most frequently affects the LE but can occur Most frequently affects the LE but can occur

anywhere.anywhere.

DiagnosisDiagnosis

►Diagnosis of exclusionDiagnosis of exclusion►Biopsy necessary to rule out infectious Biopsy necessary to rule out infectious

and vasculitic causesand vasculitic causes

Major Diagnostic CriteriaMajor Diagnostic Criteria

Rapid progression of a painful, necrolytic Rapid progression of a painful, necrolytic cutaneous ulcer with an irregular, cutaneous ulcer with an irregular, violaceous and undermined borderviolaceous and undermined border► Margin expansion of 1 to 2 cm per day or 50% increase in Margin expansion of 1 to 2 cm per day or 50% increase in

ulcer size in one monthulcer size in one month► Pain usually out or proportion to size of ulcerationPain usually out or proportion to size of ulceration► Ulcer typically preceded by a papule, pustule or bullaUlcer typically preceded by a papule, pustule or bulla

Other causes of cutaneous ulceration Other causes of cutaneous ulceration have been excludedhave been excluded► Usually necessitates skin biopsy Usually necessitates skin biopsy

Minor Diagnostic CriteriaMinor Diagnostic Criteria

History suggestive of pathergy or clinical History suggestive of pathergy or clinical finding of cribriform scarringfinding of cribriform scarring► Ulcer development at sites of minor cutaneous traumaUlcer development at sites of minor cutaneous trauma

Systemic diseases associated with PGSystemic diseases associated with PG► Inflammatory bowel disease, arthritis, IgA gammopathy, or Inflammatory bowel disease, arthritis, IgA gammopathy, or

underlying malignancyunderlying malignancy

Histopathological findingsHistopathological findings► sterile dermal neutrophilia, mixed inflammation, lymphocytic sterile dermal neutrophilia, mixed inflammation, lymphocytic

vasculitisvasculitis

Treatment responseTreatment response► Rapid response to systemic steroid treatmentRapid response to systemic steroid treatment

Associated conditionsAssociated conditions

►Occur in 70% of cases of PGOccur in 70% of cases of PG Inflammatory bowel diseaseInflammatory bowel disease Seropositive or seronegative arthritisSeropositive or seronegative arthritis MyelomaMyeloma ParaproteinemiaParaproteinemia DiverticulitisDiverticulitis Malignancy (leukemia)Malignancy (leukemia)

PathologyPathology

►Mixed cellular inflammation with Mixed cellular inflammation with neutrophil predominanceneutrophil predominance

Differential DiagnosisDifferential Diagnosis

►Vascular occlusion or stasisVascular occlusion or stasis Antiphospholipid-antidoby syndromeAntiphospholipid-antidoby syndrome Livedoid vasculopathyLivedoid vasculopathy Venous stasis ulcerationVenous stasis ulceration Klippel_Trenaunay_Weber syndromeKlippel_Trenaunay_Weber syndrome Small vessel occlusive arterial diseaseSmall vessel occlusive arterial disease Type 1 cryoglobulinemiaType 1 cryoglobulinemia


►VasculitisVasculitis Wegener granulomatosisWegener granulomatosis Polyarteritis nodosaPolyarteritis nodosa Cryoglobulinemic vasculitisCryoglobulinemic vasculitis Takayasu arteritisTakayasu arteritis Leukocytoclastic vasculitisLeukocytoclastic vasculitis


►Malignant cutaneous involvementMalignant cutaneous involvement Angiocentric T-cell lymphomaAngiocentric T-cell lymphoma Anaplastic large-cell T-cell lymphomaAnaplastic large-cell T-cell lymphoma Mycosis fungoides bullosaMycosis fungoides bullosa Unspecified lymphomaUnspecified lymphoma Leukemia cutisLeukemia cutis Histiocytosis X (Langerhans cell Histiocytosis X (Langerhans cell

histiocytosis)histiocytosis)


►Primary cutaneous infectionPrimary cutaneous infection SporotrichosisSporotrichosis AspergillosisAspergillosis CryptococcosisCryptococcosis Herpes simplex type 2 virusHerpes simplex type 2 virus Cutaneous tuberculosisCutaneous tuberculosis Amebiasis cutisAmebiasis cutis ZygomycosisZygomycosis Penicillum marneffeiPenicillum marneffei


►Drug-induced & exogenous tissue injuryDrug-induced & exogenous tissue injury Munchausen syndrome and factitiousdisorderMunchausen syndrome and factitiousdisorder Hydrea-induced ulcerationHydrea-induced ulceration BromodermaBromoderma Contact vulvitisContact vulvitis Drug-induced lupusDrug-induced lupus Laxoscelism (Brown recluse spider bite)Laxoscelism (Brown recluse spider bite) Injection drug abuse with secondary infectionInjection drug abuse with secondary infection


►Other inflammatory disordersOther inflammatory disorders Cutaneous Crohn diseaseCutaneous Crohn disease Ulcerative necrobiosis lipoidcaUlcerative necrobiosis lipoidca

TreatmentTreatment

► Corticosteroids are mainstay of therapy.Corticosteroids are mainstay of therapy. Usually will have dramatic improvement after 48-72 hoursUsually will have dramatic improvement after 48-72 hours Reduced pain and decreased erythema are the most Reduced pain and decreased erythema are the most

dramatic markers of response to treatment.dramatic markers of response to treatment. Halt of enlargement, less induration and less erythema Halt of enlargement, less induration and less erythema

also occur.also occur.► Dapsone, cyclosporine, azathioprine, tacrolimus.Dapsone, cyclosporine, azathioprine, tacrolimus.► Topical treatments possible with super-potent Topical treatments possible with super-potent

steroids in some limited cases.steroids in some limited cases.► Often require prolonged course of treatment with Often require prolonged course of treatment with

slow taper of immunosuppressionslow taper of immunosuppression► Treatment of underlying disease is also often Treatment of underlying disease is also often

effectiveeffective

Reported Effective Reported Effective TreatmentsTreatments

►CorticosteroidsCorticosteroids Systemic, intralesional, topicalSystemic, intralesional, topical

►Antimicrobial agentsAntimicrobial agents Benzoyl peroxide, clofazamine, dapsone, Benzoyl peroxide, clofazamine, dapsone,

rifampicin, lymcycline, tetracycline, rifampicin, lymcycline, tetracycline, minocycline, mezlocillin, Potassium iodide, minocycline, mezlocillin, Potassium iodide, sulfapyridine, vancomycinsulfapyridine, vancomycin

Reported Effective Reported Effective TreatmentsTreatments

►Steroid-sparing immunosuppressive Steroid-sparing immunosuppressive agentsagents 5-aminosalicylic acid (topical), 6-mercaptopurine, 5-aminosalicylic acid (topical), 6-mercaptopurine,

azathioprine, cholorambucil, cyclophosphamide, cyclosporine( azathioprine, cholorambucil, cyclophosphamide, cyclosporine( systemic, topical), methotextrate, mycophenolate mofetil, systemic, topical), methotextrate, mycophenolate mofetil, nitrogen mustard (topical), tacrolimus (systemic, topical), nitrogen mustard (topical), tacrolimus (systemic, topical), melphalanmelphalan

► Immune modulationImmune modulation Infliximab, interferon-a, intravenous y-globulin, Infliximab, interferon-a, intravenous y-globulin,

plasmapheresisplasmapheresis

►MiscellaneousMiscellaneous Colchicine, nicotine (topical), sodium cromoglycate (topical)Colchicine, nicotine (topical), sodium cromoglycate (topical)

Search PubMedSearch PubMed

►Pyoderma GangrenosumPyoderma Gangrenosum Case ReportsCase Reports ReviewsReviews Differential DiagnosisDifferential Diagnosis Drug Therapy Drug Therapy

a 36 year old female with a painful, rapidly progressive breast ulcer. id case conference wednesday,...

Documents